Adverse Drug Reactions Related with Antibiotic Medicines in Malawi: A Retrospective Analysis of Prevalence and Associated Factors.

Objective: We aimed to assess the occurrence and characteristics of antibiotic-associated adverse drug reactions (ADRs) in Malawi. Methods: We retrospectively reviewed 304 patient records from medical wards in three hospitals in Southern Malawi. A global trigger tool was applied for the detection of suspected ADRs, and we used the Naranjo scale, the World Health Organization classification and the Schumock and Thornton scale for causality, seriousness and preventability assessment respectively. ADRs were also further characterized according to anatomical systems. Statistical analysis was done in STATA 14.1. The Chi-square test was used to determine the association between categorical variables and logistic regression analysis was used to measure the strength of the association between various independent variables and the occurrence of ADRs. Results: Suspected ADRs were detected in 24% (73/304) of patients, of which 1.4% were definite, 15.1% were probable and 83.6% were possible ADRs. Most of the sADRs were gastrointestinal events (42.5%), followed by: musculoskeletal (26.3%); cardiovascular (16.3%); central nervous system (13.8%; and urinary events (1.3%). About 27% of the sADRs were serious events such as convulsions. The geriatric age group (≥65 years) was more likely to experience sADRs as compared to the younger age group, with an adjusted odds ratio (aOR) of 4.53, 95% CI (2.21-9.28), P<0.001. Patients taking more than one antibiotic medicine had a higher risk of developing sADRs as compared to patients who were administered one type of antibiotic medicine, aOR 2.14, 95% CI (1.18-3.90), p < 0.012. A long hospital stay of >3days was associated with a higher risk of sADRs with aOR of 5.11, 95% CI (2.47-10.55), p < 0.001 than those who stayed ≤ 3 days in the hospital. Conclusion: We found a higher prevalence of serious sADRs associated with antibiotic medicines than reported elsewhere. This may, among others, contribute to high patient mortality, poor treatment adherence, antibiotic resistance and increased cost of care.

What is already known and why we did the study? Most health care workers and patients are less likely to voluntarily report suspected adverse drug reactions in low- and middle-income countries such as Malawi.Studies have revealed a high usage of antibiotic medicines in Malawi, but there is limited data on the associated adverse drug reactions. What did we do? We assessed the occurrence and characteristics of ADRs associated with antibiotics. What are the new findings? We found a higher prevalence (24%) of adverse drug reactions associated with antibiotic therapy than reported elsewhere using the global trigger tool.About 27.4% of the events were serious ADRs such as convulsions, arrhythmia and hypotension.We observed a higher rate of convulsions which could be a potential safety signal. What do the new findings imply? The high prevalence of serious ADRs leads to complicated treatment strategies and contribute to patient mortality, poor treatment adherence and antibiotic resistance.ADR risk factors need to be considered when prescribing and monitoring patients on antibiotic therapy.

Effect of antibiotic medicines availability on adherence to standard treatment guidelines among hospitalized adult patients in southern Malawi.

BACKGROUND: Antibiotic resistance is a global public health problem. High and inappropriate use of antibiotic therapy exacerbate the risk of antibiotic resistance. We assessed the effect of availability of antibiotic medicines on adherence to standard treatment guidelines among hospitalized adult patients in Southern Malawi. METHODS: A cross-sectional study was done to assess the availability of 16 antibiotics among the first-line recommended treatments for common bacterial infections in Malawi. Data for up to six-month duration was extracted from stock card records in Machinga and Nsanje District Hospitals and Zomba Central Hospital. This was complemented by a retrospective review of 322 patient management files from medical wards to assess adherence to the Malawi Standard Treatment Guidelines (MSTG). Investigators abstracted data such as patient demographics, diagnoses, and prescribed therapy using a data collection form that resulted in analyzing 304 patient files. Data was entered into Microsoft excel and analyzed using STATA 14.1. Point availability, stock-out duration and adherence to treatment guidelines were presented in terms of frequencies and percentages. Chi-square test or Fisher's exact test was applied to assess the association between variables and adherence to treatment guidelines. RESULTS: Point availability of antibiotics was 81.5%, 87.7%, and 42.8% for Zomba Central, Machinga and Nsanje District Hospitals respectively. Over a period of six months, 12.5% of antibiotic medicines were stocked out for at least one day at Zomba (Median stock out days = 0, (IQR 0-0 days), while 64.3% were stocked out at Machinga (Median stock out days = 21, IQR 0-31 days) and 85.7% were stocked out at Nsanje District Hospital (Median stock out days = 66.5, IQR 18-113 days). Overall, adherence to MSTG was 79.6%, (95% CI, 73.3-84.9%). By facilities, adherence to guidelines at Zomba Central Hospital was 95.9% (95% CI, 89.7-98.9%) while at Nsanje and Machinga District Hospitals was 73.2% (95% CI, 59.7-84.2%) and 54.2% (95% CI, 39.2-68.6%) respectively. Adherence to treatment guidelines was associated with health facility, presence of laboratory test results, antibiotic spectrum, and WHO-AWaRe category of the medicine, p<0.005. Adherence was lower for antibiotics that were stocked out than antibiotics that were not stocked out during the study period (63.8%, 95% CI 48.5-77.3% vs 84.4%, 95% CI 77.7-89.8%), p< 0.002. CONCLUSION: We found unstable availability of antibiotic medicines in hospitals which might contribute to the sub-optimal adherence to standard treatment guidelines. This is a setback to efforts aimed at curbing antibiotic resistance in Malawi.

A Malawian pharmaceutical response to the COVID-19 Pandemic.

The COVID-19 pandemic has elicited swift and innovative responses due to the severity of the outbreak. Higher education institutions worldwide with pharmacy programs have identified vital gaps in COVID-19 care and has undertaken proactive steps to aid in the fight against the coronavirus. In Malawi, the Kamuzu University of Health Science's Department of Pharmacy initiated the production of a modified formulation of the World Health Organization's (WHO) recommended hand sanitizer. This manufacturing venture involved mobilizing the pharmacy faculty, identifying gaps in supplies and equipment, and utilizing evidenced-based information to create a high-quality sanitation product, which passed the requirements as tested by the Malawi Bureau of Standards. The department of pharmacy is expanding their distribution of the product to meet the needs of frontline healthcare workers and vulnerable populations. With historical issues of accessing care in Malawi and with COVID-19's spread among healthcare workers, this hand sanitizer venture is vital in the public healthcare's system response. The department of pharmacy will continue to lead the pharmacy profession in Malawi to provide targeted interventions in this unprecedented time.

Human-centred design of a new microneedle-based hormonal contraceptive delivery system.

Background: It is estimated that 225 million women worldwide have an unmet need for family planning, and more than half live in low- and middle-income countries. Increasing the choice of contraceptive methods available can reduce this unmet need. Microneedle drug delivery systems represent a new technology for minimally invasive self-administration of contraceptives. We explored stakeholders' views on different aspects of a proposed microneedle-based hormonal contraceptive delivery system. The feedback was used to iteratively develop this delivery system. Methods: Focus group discussions and semi-structured interviews were conducted with potential stakeholders (women and trans males of childbearing age, their partners, and health professionals and organisations that provide family planning advice and contraception services) in Uganda, The Gambia, Malawi, and the UK, exploring concept acceptability and gathering feedback on different aspects of design and usability of the proposed delivery system. Results: Participants viewed the concept of a new, microneedle-based contraceptive favourably. In Uganda, participants were presented with 7 different prototype applicators and identified desirable features of a preferred delivery device; their input reducing the number of prototypes that were subsequently evaluated by stakeholders in The Gambia and the UK. Participants in these countries helped to identify and/or confirm the most desirable characteristics of the applicator, resulting in design consolidation into a refined concept applicator. The final, optimised applicator prototype was validated during user research in Malawi. This human-centred design approach was also used to iteratively develop an information leaflet for the device. During these user studies, other preferred aspects of a contraceptive delivery system were also evaluated, such as anatomical site of application, duration of action, and return to fertility. Conclusions: A new microneedle-based contraceptive delivery system was iteratively developed using a human-centred design approach and was favourably received by potential stakeholders. The product is now being refined for testing in pre-clinical studies.

Enhancing Pharmacovigilance in Sub-Saharan Africa Through Training and Mentoring: A GSK Pilot Initiative in Malawi.

INTRODUCTION: Pharmacovigilance (PV) systems to monitor drug and vaccine safety are often inadequate in sub-Saharan Africa. In Malawi, a PV enhancement initiative was introduced to address major barriers to PV. OBJECTIVE: The objective of this initiative was to improve reporting of adverse events (AEs) by strengthening passive safety surveillance via PV training and mentoring of local PV stakeholders and healthcare providers (HCPs) at their own healthcare facilities (HCFs). METHODS: An 18-month PV training and mentoring programme was implemented in collaboration with national stakeholders, and in partnership with the Ministry of Health, GSK and PATH. Two-day training was provided to Expanded Programme on Immunisation coordinators, identified as responsible for AE reporting, and four National Regulatory Authority representatives. Abridged PV training and mentoring were provided regularly to HCPs. Support was given in upgrading the national PV system. Key performance indicators included the number of AEs reported, transmission of AE forms, completeness of reports, serious AEs reported and timeliness of recording into VigiFlow. RESULTS: In 18 months, 443 HCPs at 61 HCFs were trained. The number of reported AEs increased from 22 (January 2000 to October 2016) to 228 (November 2016 to May 2018), enabling Malawi to become a member of the World Health Organization Programme for International Drug Monitoring. Most (98%) AE report forms contained mandatory information on reporter, event, patient and product, but under 1% were transmitted to the national PV office within 48 h. CONCLUSION: Regular PV training and mentoring of HCPs were effective in enhancing passive safety surveillance in Malawi, but the transmission of reports to the national PV centre requires further improvement.

When a medicine or vaccine is made available for use, healthcare organisations maintain regular surveillance to confirm that the medicinal product is safe and effective. The efficiency of this surveillance depends mainly on the healthcare system and medical practices in place in each country. An important element is an effective procedure for identifying and reporting any unwanted medical occurrences (adverse events) after taking a medicinal product. In countries where regular safety surveillance has not been maintained, it is important to train and mentor healthcare providers on the need to be aware of adverse events and the importance of adhering to safety reporting procedures. GSK and partners conducted a pilot project in Malawi with the aim of improving adverse event reporting by training and mentoring healthcare providers. Training sessions and continuous mentoring were conducted over 18 months, involving 443 healthcare providers at 61 healthcare facilities. There was a large increase in the number of adverse events reported: from 22 in the 16-year period before the project started to 228 during the 18-month project period. This project showed that the training and mentoring programme for healthcare providers was effective in increasing the number of adverse events reported. This enabled Malawi to join the World Health Organization's international safety reporting scheme. Other countries facing similar challenges in safety surveillance systems could benefit from a similar approach.